Author: Ivy Cheng
With the Medical Device Regulations (MDR) coming into force from 26 May 2021 and the upcoming In Vitro Diagnostics Regulations (IVDR) from 26 May 2022, the regulatory requirements are finally coming into alignment between medical devices and in vitro diagnostics (IVD) in the European Union (EU), whereas this has been in place in Australia for the last three years.
For the MDR, IVDR and Australian applications, one of the requirements is to create a technical file that contains all the information or technical documentation related to the particular medical device or IVD held by the manufacturer. This is to demonstrate that your medical device or IVD conforms to applicable and current medical device regulatory requirements for certain markets such as Australia and the EU. The requirement for a technical file is not new but there is an increased amount of technical documentation required for both medical devices and IVDs. The technical documentation for a medical device and IVD are mostly similar in content, with a few minor differences which will be outlined in this article.
The principal requirements for both medical devices and IVDs are the quality management system, risk management, meeting the essential principles of safety and performance (i.e. Essential Principles for Australia, General Safety and Performance Requirements for MDR and IVDR), design and development, manufacturing information and labelling.
In general, meeting the requirements of certain standards such as ISO 13485:2016 Medical devices – Quality management systems – Requirements for regulatory purposes, ISO 14971:2019 Medical devices – Application of risk management to medical devices; and relevant guidance documents will provide a presumption of conformity with the essential principles of safety and performance.
Design and development principles apply for both medical devices and IVDs starting with design planning, from design inputs to design outputs to verification and validation testing and capturing design changes.
Manufacturing processes and controls, description of major systems or critical processes, and description of critical assay ingredients, where relevant, are similar for both medical devices and IVDs.
There are no major differences in labelling requirements for medical devices and IVDs except for the specific symbols used to identify a medical device and/or IVD, identified by similar but separate ISO standards.
Clinical evidence is required for all medical devices and IVDs supplied in Australia and the EU, and there has been an increased level of scrutiny by regulatory authorities and notified bodies on the clinical evidence provided.
The typical requirements for a clinical investigation (or clinical trial) for both medical devices and IVDs to support safety and/or clinical performance are similar such as approvals from ethics committees; compliance with good clinical practice, ISO 14155:2020 Clinical investigation of medical devices for human subjects – Good clinical practice or Declaration of Helsinki depending on where the clinical investigation data is collected.
The clinical investigation must also comply with any applicable requirements of the local regulatory authority or national competent authority. For example, in Australia the clinical investigation must be notified to the Therapeutic Goods Administration via the Clinical Trial Notification (CTN) or Clinical Trial Approval (CTA) schemes; and in the EU, approval from the competent authority approval and inspection of investigation sites are necessary.
The main difference is in the IVD space where clinical samples used may be excess samples from a clinical investigation or acquired by different clinical investigations. If these samples are used, the informed consent process and ethics committee approvals must be appropriate before these samples can be used.
Clinical Evaluation Report vs Performance Evaluation Report
A typical Clinical Evaluation Report (CER) contains clinical data generated and held by the manufacturer for a particular medical device. The clinical data generated can be a combination of preclinical studies, clinical investigations, post-market surveillance data including complaints, recalls and corrective actions and post-market clinical follow-up. The critical part of any CER is the literature review, appraisal/analysis of data, and evaluation of State of the Art to ensure the medical device meets the essential principles of safety and performance. A point to note is that State of the Art is central to the entire clinical evaluation and is a major focus for EU CERs.
Whereas, the Performance Evaluation Report (PER) contains the clinical evidence for a particular IVD. The PER is essentially all clinical data generated for a CER as well as performance evaluation studies incorporating analytical (e.g. benchtop tests) and clinical performance (e.g., human samples) of the IVD. The results are critically evaluated along with scientific validity and clinical utility which becomes clinical evidence for an IVD.
In addition, there is a distinct focus on stability studies and specimen type used in performance evaluation studies for IVDs. Specifically, there are more requirements for stability studies such as shelf-life in-use and under specified shipping and storage conditions. Specimen type used (e.g., fresh/frozen blood, plasma, etc.) and the type of preservation additives used (e.g., K2 EDTA, Heparin, Sodium Citrate, etc.) must be clearly identified in all performance evaluation studies.
The amount of information required for a PER depends on the risk classification. Although information may be provided as a summary for lower risk IVDs, the expectation is that the performance evaluation studies must be conducted and provided when requested. For higher-risk IVDs, a detailed analysis of the analytical and clinical performance is expected in the submission documentation.